Safety and Efficacy of Hydroxyurea and Interferon in Myeloproliferative Neoplasms: A Systematic Review

Abstract

Introduction: Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET), are characterized by excessive proliferation of myeloid cells. Hydroxyurea (HU) results in lowering blood counts, whereas pegylated interferon (PEG-IFN) offers disease modification.

Objective: This systematic review focuses on evaluating the relative benefits and risks of HU and IFN in MPN management.

Methodology: Following PRISMA guidelines, randomized controlled trials, non-randomized clinical trials, and observational studies, including MPN-112, PROUD-PV, CONTINUATION-PV, and others, were systematically reviewed. All the patients included in these studies had either PV or ET and were treated with either HU or PEG-IFN. Protocol is registered on PROSPERO (Registration no: CRD42023399263). Data extraction and Quality assessment were done according to the Cochrane handbook of systematic reviews and meta-analysis.

Results: Six studies with a total of 1,012 patients with MPNs were included, of which 552 were treated with HU and 460 were given PEG-IFN. The median age ranged from 50 to 63 years for the HU group, and from 50 to 61.8 years for the PEG-IFN group, and treatment duration ranged from 12 to 36 months. The mean hematologic response rate was 65% for both HU (359/552) and PEG-IFN (299/460) groups at 12 to 24 months; however, at 36 months, a better response was seen with PEG-IFN. Hematocrit control was obtained in 65% of patients in each group.  PEG-IFN resulted in larger decreases in JAK2V617F allele burden, with a mean of about 25% vs a mean of 15% with HU. Spleen response was assessed in 604 patients, of which 49.4% (179/362) responded to PEG-IFN, and 42.6% (141/331) responded to HU. Hematologic toxicities occurred in 25% (138/552) of HU-treated patients. In the HU group, leukemic or fibrotic transformation was seen in 2% (9/552). PEG-IFN caused immune-related adverse events in 15% (69/460) of patients, common being transaminitis (4.3%), followed by thyroid toxicities (2.4%).

Conclusions: HU and Peg IFN are both associated with hematologic response in MPN; however, Peg IFN is associated with greater long-term molecular response.

Keywords: myeloproliferative neoplasm, polycythemia vera, essential thrombocythemia, hydroxycarbamide, pegylated interferon